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  • 1.
    Almroth, Henrik
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Atrial fibrillation: inflammatory and pharmacological studies2012Doctoral thesis, comprehensive summary (Other academic)
    List of papers
    1. Source of inflammatory markers in patients with atrial fibrillation
    Open this publication in new window or tab >>Source of inflammatory markers in patients with atrial fibrillation
    Show others...
    2008 (English)In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 10, p. 848-853Article in journal (Refereed) Published
    Abstract [en]

    Aims Elevated levels of C-reactive protein and other inflammatory markers have been reported in some patients with atrial fibrillation (AF). Whether this finding is related to AF per se or to other conditions remains unclear. In addition, the source of inflammatory markers is unknown. Therefore, in the present study, we sought to assess the extent and the source of inflammation in patients with AF and no other concomitant heart or inflammatory conditions.

    Methods and results The study group consisted of 29 patients referred for radiofrequency catheter ablation: 10 patients with paroxysmal AF, 8 patients with permanent AF, and 10 control patients with Wolf-Parkinson-White (WPW) syndrome and no evidence of AF (mean age 54±11 vs. 57±13 vs. 43±16). No patient had structural heart diseases or inflammatory conditions. High-sensitive C-reactive protein, interleukin-6 (IL-6), and interleukin-8 (IL-8) were assessed in blood samples from the femoral vein, right atrium, coronary sinus, and the left and right upper pulmonary veins. All samples were collected before ablation. Compared with controls and patients with paroxysmal AF, patients with permanent AF had higher plasma levels of IL-8 in the samples from the femoral vein, right atrium, and coronary sinus, but not in the samples from the pulmonary veins (median values in the femoral vein: 2.58 vs. 2.97 vs. 4.66 pg/mL, P = 0.003; right atrium: 2.30 vs. 3.06 vs. 3.93 pg/mL, P = 0.013; coronary sinus: 2.85 vs. 3.15 vs. 4.07, P = 0.016). A high-degree correlation existed between the IL-8 levels in these samples (correlation coefficient between 0.929 and 0.976, P< 0.05). No differences in the C-reactive protein and IL-6 levels were noted between the three groups of patients.

    Conclusion The normal levels of C-reactive protein and IL-6, alongwith the elevated levels of IL-8 in patients with permanent AF but not in those with paroxysmal AF, suggest a link between a low-grade inflammatory reaction and long-lasting AF. The elevated IL-8 levels in the peripheral blood, right atrium, and coronary sinus but not in the pulmonary veins suggest a possible source of inflammation in the systemic circulation.

    Place, publisher, year, edition, pages
    Oxford University Press, 2008
    Keywords
    Atrial fibrillation, Inflammation, Catheter ablation
    National Category
    Medical and Health Sciences
    Research subject
    Medicine
    Identifiers
    urn:nbn:se:oru:diva-22941 (URN)10.1093/europace/eun111 (DOI)
    Available from: 2012-05-23 Created: 2012-05-23 Last updated: 2017-12-07Bibliographically approved
    2. Atorvastatin and persistent atrial fibrillation following cardioversion: a randomized placebo-controlled multicentre study
    Open this publication in new window or tab >>Atorvastatin and persistent atrial fibrillation following cardioversion: a randomized placebo-controlled multicentre study
    Show others...
    2009 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 30, no 7, p. 827-833Article in journal (Refereed) Published
    Abstract [en]

    AIMS: To evaluate the effect of atorvastatin in achieving stable sinus rhythm (SR) 30 days after electrical cardioversion (CV) in patients with persistent atrial fibrillation (AF). METHODS AND RESULTS: The study included 234 patients. The patients were randomized to treatment with atorvastatin 80 mg daily (n = 118) or placebo (n = 116) in a prospective, double-blinded fashion. Treatment was initiated 14 days before CV and was continued 30 days after CV. The two groups were well-balanced with respect to baseline characteristics. Mean age was 65 +/- 10 years, 76% of the patients were male and 4% had ischaemic heart disease. Study medication was well-tolerated in all patients but one. Before primary endpoint 12 patients were excluded. In the atorvastatin group 99 patients (89%) converted to SR at electrical CV compared with 95 (86%) in the placebo group (P = 0.42). An intention-to-treat analysis with the available data, by randomization group, showed that 57 (51%) in the atorvastatin group and 47 (42%) in the placebo group were in SR 30 days after CV (OR 1.44, 95%CI 0.85-2.44, P = 0.18). CONCLUSION: Atorvastatin was not statistically superior to placebo with regards to maintaining SR 30 days after CV in patients with persistent AF.

    Place, publisher, year, edition, pages
    Philadelphia: W.B. Saunders, 2009
    National Category
    Medical and Health Sciences Cardiac and Cardiovascular Systems
    Research subject
    Cardiology
    Identifiers
    urn:nbn:se:oru:diva-11644 (URN)10.1093/eurheartj/ehp006 (DOI)19202157 (PubMedID)
    Available from: 2010-08-27 Created: 2010-08-27 Last updated: 2017-12-12Bibliographically approved
    3. The safety of flecainide treatment of atrial fibrillation: long-term incidence of sudden cardiac death and proarrhythmic events
    Open this publication in new window or tab >>The safety of flecainide treatment of atrial fibrillation: long-term incidence of sudden cardiac death and proarrhythmic events
    Show others...
    2011 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 270, no 3, p. 281-290Article in journal (Refereed) Published
    Abstract [en]

    Objective:To assess the safety of long-term treatment with flecainide in patients with atrial fibrillation (AF), particularly with regard to sudden cardiac death (SCD) andproarrhythmic events.

    Design: Retrospective,observational cohort study.Setting.Single-centre study at Örebro University Hospital, Sweden.

    Setting: Single-centre study at Orebro University Hospital, Sweden.

    Subjects: A total of 112 patients with paroxysmal (51%) or persistent (49%) AF (mean age 60 ± 11 years) were included after identifying all patients with AF who initiated oral flecainide treatment (mean dose 203 ± 43 mg per day) between 1998 and 2006. Standard exclusion⁄inclusion criteria for flecainide were used,andflecainidetreatmentwasusually combined withanatrioventricular-blocking agent (89%).

    Main outcome measure: Death was classified as sudden or nonsudden according to standard definitions. Proarrhythmia was defined as cardiac syncope or lifethreatening arrhythmia.

    Results: Eight deaths were reported during a mean follow- up of 3.4 ± .4 years. Compared to the general population, the standardized mortality ratios were 1.57 (95% confidence interval (CI) 0.68–3.09) for allcause mortality and 4.16 (95% CI 1.53–9.06) for death from cardiovascular disease. Three deaths were classified as SCDs. Proarrhythmic events occurred in six patients (two each with wide QRS tachycardia, 1 : 1 conducted atrial flutter and syncope during exercise).

    Conclusion: We found an increased incidence of SCD or proarrhythmic events in this real-world study of flecainide used for the treatment of AF. The findings suggest that further investigation into the safety of flecainide for the treatment of patients with AF is warranted.

    Place, publisher, year, edition, pages
    John Wiley & Sons, 2011
    Keywords
    atrial fibrillation, flecainide, proarrhythmia, safety, sudden cardiac death
    National Category
    General Practice
    Identifiers
    urn:nbn:se:oru:diva-22942 (URN)10.1111/j.1365-2796.2011.02395.x (DOI)000293793600011 ()21635583 (PubMedID)2-s2.0-80051576394 (Scopus ID)
    Note

    Funding Agencies:

    Boehringer-Ingelheim  

    Sanofi-Aventis  

    Astra Zeneca  

    Bristol-Myers Squibb 

    Available from: 2012-05-23 Created: 2012-05-23 Last updated: 2018-09-11Bibliographically approved
    4. Safety of flecainide for atrial fibrillation: the Swedish atrial fibrillation cohort study
    Open this publication in new window or tab >>Safety of flecainide for atrial fibrillation: the Swedish atrial fibrillation cohort study
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background Little is known about the safety of flecainide in atrial fibrillation (AF). Whether current flecainide treatment practice in Sweden is associated with increased mortality compared to treatment with beta-blockers alone was investigated in patients with atrial fibrillation (AF).

    Methods and Results A total of 182,678 patients diagnosed with AF between 1 July 2005 and 31 December 2008 were identified through the Swedish National Hospital Discharge Register. These data were matched to data from the Prescribed Drug Register and information about death from the Total Population Register. The primary outcome was all cause mortality at the end of the study period, 1 Feb 2010. Flecainide was prescribed to 5381 patients (2.9%), and 64,918 patients (45.7%) received beta-blockers only. During follow-up, 2.8% and 30.8% of these patients died, respectively. After coarsened and exact matching, 2,178 patients (1.2% of total) on flecainide and beta-blockers had more similar baseline characteristics to 27,313 patients (15.3% of total) on beta-blockers only. In the main analysis, flecainide exposure was not associated with increased mortality (OR 0.27, 95% CI 0.21-0.36,P<0.001). In the matched flecainide population, 205 (9.4%) patients had underlying structural heart disease. Sixteen (28.6%) of the flecainide-exposed patients who died had structural heart disease. The patients who only received flecainide (n=264) had higher mortality rate than the patients who received flecainide and beta-blockers (6.8 versus 2.6%,P<0.001).

    Conclusions Flecainide is not associated with increased mortality in patients with AF compared to beta-blockers alone. Patients who die after receiving flecainide often have structural heart disease.

    National Category
    Medical and Health Sciences
    Research subject
    Medicine
    Identifiers
    urn:nbn:se:oru:diva-22943 (URN)
    Available from: 2012-05-23 Created: 2012-05-23 Last updated: 2017-10-17Bibliographically approved
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  • 2.
    Almroth, Henrik
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Andersson, Torbjorn
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Fengsrud, Espen
    Örebro University, School of Health Sciences. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Friberg, Leif
    Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Linde, P.
    Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Rosenqvist, Mårten
    Stockholm South Hospital, Karolinska Institutet, Stockholm, Sweden.
    Englund, A.
    Stockholm South Hospital, Karolinska Institutet, Stockholm, Sweden.
    The safety of flecainide treatment of atrial fibrillation: long-term incidence of sudden cardiac death and proarrhythmic events2011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 270, no 3, p. 281-290Article in journal (Refereed)
    Abstract [en]

    Objective:To assess the safety of long-term treatment with flecainide in patients with atrial fibrillation (AF), particularly with regard to sudden cardiac death (SCD) andproarrhythmic events.

    Design: Retrospective,observational cohort study.Setting.Single-centre study at Örebro University Hospital, Sweden.

    Setting: Single-centre study at Orebro University Hospital, Sweden.

    Subjects: A total of 112 patients with paroxysmal (51%) or persistent (49%) AF (mean age 60 ± 11 years) were included after identifying all patients with AF who initiated oral flecainide treatment (mean dose 203 ± 43 mg per day) between 1998 and 2006. Standard exclusion⁄inclusion criteria for flecainide were used,andflecainidetreatmentwasusually combined withanatrioventricular-blocking agent (89%).

    Main outcome measure: Death was classified as sudden or nonsudden according to standard definitions. Proarrhythmia was defined as cardiac syncope or lifethreatening arrhythmia.

    Results: Eight deaths were reported during a mean follow- up of 3.4 ± .4 years. Compared to the general population, the standardized mortality ratios were 1.57 (95% confidence interval (CI) 0.68–3.09) for allcause mortality and 4.16 (95% CI 1.53–9.06) for death from cardiovascular disease. Three deaths were classified as SCDs. Proarrhythmic events occurred in six patients (two each with wide QRS tachycardia, 1 : 1 conducted atrial flutter and syncope during exercise).

    Conclusion: We found an increased incidence of SCD or proarrhythmic events in this real-world study of flecainide used for the treatment of AF. The findings suggest that further investigation into the safety of flecainide for the treatment of patients with AF is warranted.

  • 3.
    Almroth, Henrik
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Friberg, Leif
    Unit of Cardiology, Karolinska Institutet, Dept of Clinical Sciences, Danderyd Hospital, Sweden.
    Bodin, Lennart
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Rosenqvist, Mårten
    Dept of Clinical Science and Education, Södersjukhuset, Unit of Cardiology, Karolinska Institutet at Stockholm, Sweden.
    Englund, Anders
    Dept of Clinical Science and Education, Södersjukhuset, Unit of Cardiology, Karolinska Institutet at Stockholm, Sweden.
    Safety of flecainide for atrial fibrillation: the Swedish atrial fibrillation cohort studyManuscript (preprint) (Other academic)
    Abstract [en]

    Background Little is known about the safety of flecainide in atrial fibrillation (AF). Whether current flecainide treatment practice in Sweden is associated with increased mortality compared to treatment with beta-blockers alone was investigated in patients with atrial fibrillation (AF).

    Methods and Results A total of 182,678 patients diagnosed with AF between 1 July 2005 and 31 December 2008 were identified through the Swedish National Hospital Discharge Register. These data were matched to data from the Prescribed Drug Register and information about death from the Total Population Register. The primary outcome was all cause mortality at the end of the study period, 1 Feb 2010. Flecainide was prescribed to 5381 patients (2.9%), and 64,918 patients (45.7%) received beta-blockers only. During follow-up, 2.8% and 30.8% of these patients died, respectively. After coarsened and exact matching, 2,178 patients (1.2% of total) on flecainide and beta-blockers had more similar baseline characteristics to 27,313 patients (15.3% of total) on beta-blockers only. In the main analysis, flecainide exposure was not associated with increased mortality (OR 0.27, 95% CI 0.21-0.36,P<0.001). In the matched flecainide population, 205 (9.4%) patients had underlying structural heart disease. Sixteen (28.6%) of the flecainide-exposed patients who died had structural heart disease. The patients who only received flecainide (n=264) had higher mortality rate than the patients who received flecainide and beta-blockers (6.8 versus 2.6%,P<0.001).

    Conclusions Flecainide is not associated with increased mortality in patients with AF compared to beta-blockers alone. Patients who die after receiving flecainide often have structural heart disease.

  • 4.
    Almroth, Henrik
    et al.
    Örebro University, School of Health and Medical Sciences.
    Höglund, Niklas
    Boman, Kurt
    Englund, Anders
    Jensen, Steen
    Kjellman, Björn
    Tornvall, Per
    Rosenqvist, Mårten
    Atorvastatin and persistent atrial fibrillation following cardioversion: a randomized placebo-controlled multicentre study2009In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 30, no 7, p. 827-833Article in journal (Refereed)
    Abstract [en]

    AIMS: To evaluate the effect of atorvastatin in achieving stable sinus rhythm (SR) 30 days after electrical cardioversion (CV) in patients with persistent atrial fibrillation (AF). METHODS AND RESULTS: The study included 234 patients. The patients were randomized to treatment with atorvastatin 80 mg daily (n = 118) or placebo (n = 116) in a prospective, double-blinded fashion. Treatment was initiated 14 days before CV and was continued 30 days after CV. The two groups were well-balanced with respect to baseline characteristics. Mean age was 65 +/- 10 years, 76% of the patients were male and 4% had ischaemic heart disease. Study medication was well-tolerated in all patients but one. Before primary endpoint 12 patients were excluded. In the atorvastatin group 99 patients (89%) converted to SR at electrical CV compared with 95 (86%) in the placebo group (P = 0.42). An intention-to-treat analysis with the available data, by randomization group, showed that 57 (51%) in the atorvastatin group and 47 (42%) in the placebo group were in SR 30 days after CV (OR 1.44, 95%CI 0.85-2.44, P = 0.18). CONCLUSION: Atorvastatin was not statistically superior to placebo with regards to maintaining SR 30 days after CV in patients with persistent AF.

  • 5.
    Bergh, Cecilia
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Udumyan, Ruzan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Fall, Katja
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Almroth, Henrik
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Montgomery, Scott
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, United Kingdom .
    Stress resilience and physical fitness in adolescence and risk of coronary heart disease in middle age2015In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 101, no 8, p. 623-629Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Psychosocial stress is a suggested risk for coronary heart disease (CHD). The relationship of stress resilience in adolescence with subsequent CHD risk is underinvestigated, so our objective was to assess this and investigate the possible mediating role of physical fitness.

    METHODS: In this register-based study, 237 980 men born between 1952 and 1956 were followed from 1987 to 2010 using information from Swedish registers. Stress resilience was measured at a compulsory military conscription examination using a semistructured interview with a psychologist. Some 10 581 diagnoses of CHD were identified. Cox regression estimated the association of stress resilience with CHD, with adjustment for established cardiovascular risk factors.

    RESULTS: Low-stress resilience was associated with increased CHD risk. The association remained after adjustment for physical fitness and other potential confounding and mediating factors, with adjusted HRs (and 95% CIs) of 1.17 (1.10 to 1.25), with some evidence of mediation by physical fitness. CHD incidence rates per 1000 person-years (and 95% CIs) for low-stress, medium-stress and high-stress resilience were 2.61 (2.52 to 2.70), 1.97 (1.92 to 2.03) and 1.59 (1.53 to 1.67) respectively. Higher physical fitness was inversely associated with CHD risk; however, this was attenuated by low-stress resilience, shown by interaction testing (p<0.001).

    CONCLUSIONS: Low-stress resilience in adolescence was associated with increased risk of CHD in middle age and may diminish the benefit of physical fitness. This represents new evidence of the role of stress resilience in determining risk of CHD and its interrelationship with physical fitness.

  • 6. Jons, Christian
    et al.
    Steen Hansen, Peter
    Johannessen, Arne
    Hindricks, Gerhard
    Raatikainen, Pekka
    Kongstad, Ole
    Walfridsson, Håkan
    Pehrson, Steen
    Almroth, Henrik
    Örebro University, School of Health and Medical Sciences.
    Hartikainen, Juha
    Petersen, Anders Kirstein
    Spange Mortensen, Leif
    Cosedis Nielsen, Jens
    The Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial: clinical rationale, study design, and implementation2009In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 11, no 7, p. 917-923Article in journal (Refereed)
    Abstract [en]

    AIMS: No large randomized multicentre trial has evaluated the efficacy of radiofrequency ablation (RFA) vs. anti-arrhythmic drug (AAD) therapy as a first-line treatment of paroxysmal atrial fibrillation (AF). METHODS AND RESULTS: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation (MANTRA-PAF) trial is a randomized, controlled, parallel group, multicentre study designed to test whether catheter-based RFA is superior to optimized AAD therapy in suppressing relapse within 24 months of symptomatic and/or asymptomatic AF in patients with paroxysmal AF without prior AAD therapy. The primary endpoint is cumulative AF burden on repeated 7 days Holter monitoring. Secondary endpoints are: thromboembolic events, hospitalization due to arrhythmia, pro-arrhythmic events, procedure/treatment-related side effects, health economics, quality of life, and change in left ventricular function. Ten centres in Scandinavia and Germany are participating in the study. Enrolment was started in 2005 and as of November 2008, 260 patients have been enrolled into the study. It is expected that enrolment will end by March 2009, when 300 patients have been included. CONCLUSION: The MANTRA-PAF trial will determine whether catheter-based RFA is superior to optimized AAD therapy as a first-line treatment in suppressing long-term relapse of symptomatic and/or asymptomatic AF.

  • 7.
    Liuba, Ioan
    et al.
    Department of Cardiology, University Hospital Linköping, 581 85 Linköp.
    Almroth, Henrik
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Jonasson, Lena
    Department of Cardiology, University Hospital Linköping, 581 85 Linköp.
    Englund, Anders
    Department of Cardiology, University Hospital Örebro, Örebro, Sweden.
    Jönsson, Anders
    Department of Cardiology, University Hospital Linköping, 581 85 Linköping, Sweden.
    Säfström, Kåge
    Department of Cardiology, University Hospital Linköping, 581 85 Linköping, Sweden.
    Walfridsson, Håkan
    Department of Cardiology, University Hospital Linköping, 581 85 Linköping, Sweden.
    Source of inflammatory markers in patients with atrial fibrillation2008In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 10, p. 848-853Article in journal (Refereed)
    Abstract [en]

    Aims Elevated levels of C-reactive protein and other inflammatory markers have been reported in some patients with atrial fibrillation (AF). Whether this finding is related to AF per se or to other conditions remains unclear. In addition, the source of inflammatory markers is unknown. Therefore, in the present study, we sought to assess the extent and the source of inflammation in patients with AF and no other concomitant heart or inflammatory conditions.

    Methods and results The study group consisted of 29 patients referred for radiofrequency catheter ablation: 10 patients with paroxysmal AF, 8 patients with permanent AF, and 10 control patients with Wolf-Parkinson-White (WPW) syndrome and no evidence of AF (mean age 54±11 vs. 57±13 vs. 43±16). No patient had structural heart diseases or inflammatory conditions. High-sensitive C-reactive protein, interleukin-6 (IL-6), and interleukin-8 (IL-8) were assessed in blood samples from the femoral vein, right atrium, coronary sinus, and the left and right upper pulmonary veins. All samples were collected before ablation. Compared with controls and patients with paroxysmal AF, patients with permanent AF had higher plasma levels of IL-8 in the samples from the femoral vein, right atrium, and coronary sinus, but not in the samples from the pulmonary veins (median values in the femoral vein: 2.58 vs. 2.97 vs. 4.66 pg/mL, P = 0.003; right atrium: 2.30 vs. 3.06 vs. 3.93 pg/mL, P = 0.013; coronary sinus: 2.85 vs. 3.15 vs. 4.07, P = 0.016). A high-degree correlation existed between the IL-8 levels in these samples (correlation coefficient between 0.929 and 0.976, P< 0.05). No differences in the C-reactive protein and IL-6 levels were noted between the three groups of patients.

    Conclusion The normal levels of C-reactive protein and IL-6, alongwith the elevated levels of IL-8 in patients with permanent AF but not in those with paroxysmal AF, suggest a link between a low-grade inflammatory reaction and long-lasting AF. The elevated IL-8 levels in the peripheral blood, right atrium, and coronary sinus but not in the pulmonary veins suggest a possible source of inflammation in the systemic circulation.

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